Postoperative Nausea and Vomiting
Conditions
Keywords
PONV, nausea, emesis, antiemetics, aprepitant, ondansetron, dexamethasone
Brief summary
We hypothesize that the combination of aprepitant with dexamethasone will provide significantly improved prophylaxis against Postoperative nausea and vomiting compared with the combination of ondansetron and dexamethasone, in patients undergoing craniotomy under general anesthesia.
Interventions
Aprepitant 40 mg + Dexamethasone 10 mg
Ondansetron 4 mg + Dexamethasone 10 mg
Sponsors
Merck Sharp & Dohme LLC
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
A patient is eligible for inclusion in this study if all of the following criteria apply: * Age: 18-75 years of age * Surgery: craniotomy under general anesthesia. * American Society of Anesthesiologists (ASA) Status: ASA: I, II, or III * Language: Fluent in the English language * Informed Consent: Written informed consent must be obtained.
Exclusion criteria
A patient will not be eligible for inclusion in this study if any one or more of the following criteria apply within thirty days of patient enrollment in this clinical trial: * Medical: Any condition that may impair a patient's ability to complete any of the study assessments or confound interpretation of results. * Hypersensitivity: Patient has a known immediate or delayed hypersensitivity reaction or known idiosyncrasy to any of the two study medications, ondansetron, or aprepitant. * Other Drugs: Patients should not be taking medications with known antiemetic properties (phenothiazines, butyrophenones, antihistamines), nor should they receive metoclopramide, or other antiemetics preoperatively or 12 hours before the scheduled surgical procedure. * Pregnant or lactating females: A pregnancy test will be performed within 24 hours of entering the study for females of childbearing potential. * Substance Abuse: Clinically significant abuse of substances (alcohol, illicit or prescribed medications) such that the patient is unable to provide informed consent or reliably complete any of the study assessments. * Psychiatric Disease: History of a psychiatric illness that may impair the patient's ability to provide informed consent or complete any of the study assessments. * Nausea verbal rating score (VRS): A VRS nausea score \> 3 (scale 0-10) in the preoperative holding area before pretreatment with the study medications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Emesis | 48 h | Any vomiting or retching |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Vomiting (Post OP) | Post OP (0 - 2 hours) | — |
| Incidence of Vomiting (24 Hours) | 24 h | Any vomiting or retching |
| Use of Rescue Antiemetics (Post OP) | Post OP (0 - 2 hours) | — |
| Use of Rescue Antiemetics (24 Hours) | 24 h | — |
| Use of Rescue Antiemetics (48 Hours) | 48 hour | — |
| Incidence of Nausea | Post operative procedure (OP) hours (0-2, 24, 48) | operative procedure |
| Average Nausea Score | Post OP hours 0-2, 24 h, 48 h | Participants verbally rated their nausea on a scale of 0-10. 0 = No nausea, 10 = worst nausea imaginable |
| Number of Vomiting Episodes | 48 hours | — |
| Time to First Vomiting | 48 h | — |
| Number of Participants Who Rated Their Satisfaction With Antiemetic Management as Very Satisfied | 48 hour | Participants rated their satisfaction with antiemetic management on a 5 points scale: very satisfied, somewhat satisfied, neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied) |
| Number of Participants With a Complete Response Rate | 24 hours Post OP, 48 hours Post OP | complete response rate: defined as no Postoperative nausea and vomiting (PONV) and no need for rescue antiemetics. |
Countries
United States
Participant flow
Recruitment details
The study took place at Duke University Medical Center from September 2007 to June 2009, 146 signed the consent form, 115 were randomized, 104 completed the study
Participants by arm
| Arm | Count |
|---|---|
| Aprepitant Aprepitant 40 mg preoperatively + dexamethasone 10 mg after induction of anesthesia | 57 |
| Ondansetron Ondansetron 4 mg within 30 minutes of the end of surgery + Dexamethasone 10 mg after induction of anesthesia | 58 |
| Total | 115 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | No intervention/ screen fail | 5 | 3 |
Baseline characteristics
| Characteristic | Ondansetron | Aprepitant | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 58 Participants | 57 Participants | 115 Participants |
| Age, Continuous | 48 years STANDARD_DEVIATION 13 | 51 years STANDARD_DEVIATION 13 | 50 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 58 participants | 57 participants | 115 participants |
| Sex/Gender, Customized Female | 30 participants | 34 participants | 64 participants |
| Sex/Gender, Customized Male | 29 participants | 22 participants | 51 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 51 | 0 / 53 |
| serious Total, serious adverse events | 0 / 51 | 0 / 53 |
Outcome results
Primary
Cumulative Incidence of Emesis
Any vomiting or retching
Time frame: 48 h
Population: ITT analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Cumulative Incidence of Emesis | 8 participants |
| Ondansetron | Cumulative Incidence of Emesis | 20 participants |
Secondary
Average Nausea Score
Participants verbally rated their nausea on a scale of 0-10. 0 = No nausea, 10 = worst nausea imaginable
Time frame: Post OP hours 0-2, 24 h, 48 h
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Aprepitant | Average Nausea Score | 0-2 hours post op | 0.4 units on a scale |
| Aprepitant | Average Nausea Score | 24 hours post op | 0.8 units on a scale |
| Aprepitant | Average Nausea Score | 48 hours post op | 0.9 units on a scale |
| Ondansetron | Average Nausea Score | 0-2 hours post op | 0.6 units on a scale |
| Ondansetron | Average Nausea Score | 24 hours post op | 1.3 units on a scale |
| Ondansetron | Average Nausea Score | 48 hours post op | 1.1 units on a scale |
Secondary
Incidence of Nausea
operative procedure
Time frame: Post operative procedure (OP) hours (0-2, 24, 48)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aprepitant | Incidence of Nausea | 0-2 hours Post OP | 27 participants |
| Aprepitant | Incidence of Nausea | 24 Hours Post Op | 33 participants |
| Aprepitant | Incidence of Nausea | 48 Hours Post Op | 35 participants |
| Ondansetron | Incidence of Nausea | 0-2 hours Post OP | 27 participants |
| Ondansetron | Incidence of Nausea | 24 Hours Post Op | 30 participants |
| Ondansetron | Incidence of Nausea | 48 Hours Post Op | 32 participants |
Secondary
Incidence of Vomiting (24 Hours)
Any vomiting or retching
Time frame: 24 h
Population: ITT analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Incidence of Vomiting (24 Hours) | 7 participants |
| Ondansetron | Incidence of Vomiting (24 Hours) | 19 participants |
Secondary
Incidence of Vomiting (Post OP)
Time frame: Post OP (0 - 2 hours)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Incidence of Vomiting (Post OP) | 3 participants |
| Ondansetron | Incidence of Vomiting (Post OP) | 11 participants |
Secondary
Number of Participants Who Rated Their Satisfaction With Antiemetic Management as Very Satisfied
Participants rated their satisfaction with antiemetic management on a 5 points scale: very satisfied, somewhat satisfied, neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied)
Time frame: 48 hour
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Number of Participants Who Rated Their Satisfaction With Antiemetic Management as Very Satisfied | 36 participants |
| Ondansetron | Number of Participants Who Rated Their Satisfaction With Antiemetic Management as Very Satisfied | 32 participants |
Secondary
Number of Participants With a Complete Response Rate
complete response rate: defined as no Postoperative nausea and vomiting (PONV) and no need for rescue antiemetics.
Time frame: 24 hours Post OP, 48 hours Post OP
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aprepitant | Number of Participants With a Complete Response Rate | 24 Hours Post OP | 14 participants |
| Aprepitant | Number of Participants With a Complete Response Rate | 48 Hours Post OP | 11 participants |
| Ondansetron | Number of Participants With a Complete Response Rate | 24 Hours Post OP | 21 participants |
| Ondansetron | Number of Participants With a Complete Response Rate | 48 Hours Post OP | 19 participants |
Secondary
Number of Vomiting Episodes
Time frame: 48 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Aprepitant | Number of Vomiting Episodes | 0 vomiting episodes |
| Ondansetron | Number of Vomiting Episodes | 0 vomiting episodes |
Secondary
Time to First Vomiting
Time frame: 48 h
Population: The analysis population only includes participants who had vomiting and had a complete data set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Aprepitant | Time to First Vomiting | 13.5 hours |
| Ondansetron | Time to First Vomiting | 2 hours |
Secondary
Use of Rescue Antiemetics (24 Hours)
Time frame: 24 h
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Use of Rescue Antiemetics (24 Hours) | 31 participants |
| Ondansetron | Use of Rescue Antiemetics (24 Hours) | 30 participants |
Secondary
Use of Rescue Antiemetics (48 Hours)
Time frame: 48 hour
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Use of Rescue Antiemetics (48 Hours) | 33 participants |
| Ondansetron | Use of Rescue Antiemetics (48 Hours) | 32 participants |
Secondary
Use of Rescue Antiemetics (Post OP)
Time frame: Post OP (0 - 2 hours)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Use of Rescue Antiemetics (Post OP) | 20 participants |
| Ondansetron | Use of Rescue Antiemetics (Post OP) | 24 participants |